Homo sapiens
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PROVIDER: PRJNA293096 | ENA |
REPOSITORIES: ENA
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Project description:Resveratrol is a natural product that has gained tremendous interest due to multiple reported health-beneficial effects. However, the underlying mechanisms of action of this compound remained largely controversial. Here, we demonstrate that major biological effects of resveratrol might be attributed to its bicarbonate-induced production of phenolic radicals and reactive oxygen species (ROS) such as superoxide and hydrogen peroxide under physiologically relevant conditions. These products derived from low hormetic micromolar concentrations of resveratrol led to gene expression reprogramming, which was mainly controlled by the redox-sensitive transcription factor nuclear factor (erythroid-derived 2) like 2 (Nrf2), whereas too high concentrations of resveratrol became detrimental for cells. Gentle but significant activation of Nrf2-controlled gene expression resulted in a metabolic switch and reduced cellular redox environment. Thereby cells could be preconditioned against stress, for example to protect primary keratinocytes of the human epidermis from oxidative stress that was induced by metabolization of ethanol. Hormetic shifting of cells by chemical triggers such as resveratrol towards a more reductive state might represent a powerful conceptual framework to improve cellular fitness at low nontoxic concentrations. Total RNA obtained from cultured primary neonatal normal human epidermal keratinocytes (NHEK) subjected to 16 hours treatment with 50 µM resveratrol (trans-3,5,4â-trihydroxystilbene, RSV) compared to vehicle-treated control NHEKs.
2015-12-31 | E-GEOD-72119 | biostudies-arrayexpress
Project description:Resveratrol is a natural product that has gained tremendous interest due to multiple reported health-beneficial effects. However, the underlying mechanisms of action of this compound remained largely controversial. Here, we demonstrate that major biological effects of resveratrol might be attributed to its bicarbonate-induced production of phenolic radicals and reactive oxygen species (ROS) such as superoxide and hydrogen peroxide under physiologically relevant conditions. These products derived from low hormetic micromolar concentrations of resveratrol led to gene expression reprogramming, which was mainly controlled by the redox-sensitive transcription factor nuclear factor (erythroid-derived 2) like 2 (Nrf2), whereas too high concentrations of resveratrol became detrimental for cells. Gentle but significant activation of Nrf2-controlled gene expression resulted in a metabolic switch and reduced cellular redox environment. Thereby cells could be preconditioned against stress, for example to protect primary keratinocytes of the human epidermis from oxidative stress that was induced by metabolization of ethanol. Hormetic shifting of cells by chemical triggers such as resveratrol towards a more reductive state might represent a powerful conceptual framework to improve cellular fitness at low nontoxic concentrations.
2015-12-31 | GSE72119 | GEO
Project description:Martinez-Guimera2017 - Generic redox signalling model without negative regulation (Model 1)
This model is described in the article:
'Molecular habituation' as a
potential mechanism of gradual homeostatic loss with age.
Martinez Guimera A, Welsh CM,
Proctor CJ, McArdle A, Shanley DP.
Mech. Ageing Dev. 2017 Nov; :
Abstract:
The ability of reactive oxygen species (ROS) to cause
molecular damage has meant that chronic oxidative stress has
been mostly studied from the point of view of being a source of
toxicity to the cell. However, the known duality of ROS
molecules as both damaging agents and cellular redox signals
implies another perspective in the study of sustained oxidative
stress. This is a perspective of studying oxidative stress as a
constitutive signal within the cell. In this work, we adopt a
theoretical perspective as an exploratory and explanatory
approach to examine how chronic oxidative stress can interfere
with signal processing by redox signalling pathways in the
cell. We report that constitutive signals can give rise to a
'molecular habituation' effect that can prime for a gradual
loss of biological function. This is because a constitutive
signal in the environment has the potential to reduce the
responsiveness of a signalling pathway through the prolonged
activation of negative regulators. Additionally, we demonstrate
how this phenomenon is likely to occur in different signalling
pathways exposed to persistent signals and furthermore at
different levels of biological organisation.
This model is hosted on
BioModels Database
and identified by:
MODEL1710260000.
To cite BioModels Database, please use:
Chelliah V et al. BioModels: ten-year
anniversary. Nucl. Acids Res. 2015, 43(Database
issue):D542-8.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
CC0
Public Domain Dedication for more information.
| MODEL1710260000 | BioModels
Project description:Martinez-Guimera2017 - Generic redox signalling model with negative feedback regulation (Model 2)
This model is described in the article:
'Molecular habituation' as a
potential mechanism of gradual homeostatic loss with age.
Martinez Guimera A, Welsh CM,
Proctor CJ, McArdle A, Shanley DP.
Mech. Ageing Dev. 2017 Nov; :
Abstract:
The ability of reactive oxygen species (ROS) to cause
molecular damage has meant that chronic oxidative stress has
been mostly studied from the point of view of being a source of
toxicity to the cell. However, the known duality of ROS
molecules as both damaging agents and cellular redox signals
implies another perspective in the study of sustained oxidative
stress. This is a perspective of studying oxidative stress as a
constitutive signal within the cell. In this work, we adopt a
theoretical perspective as an exploratory and explanatory
approach to examine how chronic oxidative stress can interfere
with signal processing by redox signalling pathways in the
cell. We report that constitutive signals can give rise to a
'molecular habituation' effect that can prime for a gradual
loss of biological function. This is because a constitutive
signal in the environment has the potential to reduce the
responsiveness of a signalling pathway through the prolonged
activation of negative regulators. Additionally, we demonstrate
how this phenomenon is likely to occur in different signalling
pathways exposed to persistent signals and furthermore at
different levels of biological organisation.
This model is hosted on
BioModels Database
and identified by:
MODEL1710260001.
To cite BioModels Database, please use:
Chelliah V et al. BioModels: ten-year
anniversary. Nucl. Acids Res. 2015, 43(Database
issue):D542-8.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
CC0
Public Domain Dedication for more information.
| MODEL1710260001 | BioModels
Project description:Martinez-Guimera2017 - Generic redox signalling model with negative feedforward regulation (Model 3)
This model is described in the article:
'Molecular habituation' as a
potential mechanism of gradual homeostatic loss with age.
Martinez Guimera A, Welsh CM,
Proctor CJ, McArdle A, Shanley DP.
Mech. Ageing Dev. 2017 Nov; :
Abstract:
The ability of reactive oxygen species (ROS) to cause
molecular damage has meant that chronic oxidative stress has
been mostly studied from the point of view of being a source of
toxicity to the cell. However, the known duality of ROS
molecules as both damaging agents and cellular redox signals
implies another perspective in the study of sustained oxidative
stress. This is a perspective of studying oxidative stress as a
constitutive signal within the cell. In this work, we adopt a
theoretical perspective as an exploratory and explanatory
approach to examine how chronic oxidative stress can interfere
with signal processing by redox signalling pathways in the
cell. We report that constitutive signals can give rise to a
'molecular habituation' effect that can prime for a gradual
loss of biological function. This is because a constitutive
signal in the environment has the potential to reduce the
responsiveness of a signalling pathway through the prolonged
activation of negative regulators. Additionally, we demonstrate
how this phenomenon is likely to occur in different signalling
pathways exposed to persistent signals and furthermore at
different levels of biological organisation.
This model is hosted on
BioModels Database
and identified by:
MODEL1710260002.
To cite BioModels Database, please use:
Chelliah V et al. BioModels: ten-year
anniversary. Nucl. Acids Res. 2015, 43(Database
issue):D542-8.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
CC0
Public Domain Dedication for more information.
| MODEL1710260002 | BioModels
Project description:Martinez-Guimera2017 - Generic redox signalling model with negative feedback regulation (Model 2)
This model is described in the article:
'Molecular habituation' as a
potential mechanism of gradual homeostatic loss with age.
Martinez Guimera A, Welsh CM,
Proctor CJ, McArdle A, Shanley DP.
Mech. Ageing Dev. 2017 Nov; :
Abstract:
The ability of reactive oxygen species (ROS) to cause
molecular damage has meant that chronic oxidative stress has
been mostly studied from the point of view of being a source of
toxicity to the cell. However, the known duality of ROS
molecules as both damaging agents and cellular redox signals
implies another perspective in the study of sustained oxidative
stress. This is a perspective of studying oxidative stress as a
constitutive signal within the cell. In this work, we adopt a
theoretical perspective as an exploratory and explanatory
approach to examine how chronic oxidative stress can interfere
with signal processing by redox signalling pathways in the
cell. We report that constitutive signals can give rise to a
'molecular habituation' effect that can prime for a gradual
loss of biological function. This is because a constitutive
signal in the environment has the potential to reduce the
responsiveness of a signalling pathway through the prolonged
activation of negative regulators. Additionally, we demonstrate
how this phenomenon is likely to occur in different signalling
pathways exposed to persistent signals and furthermore at
different levels of biological organisation.
This model is hosted on
BioModels Database
and identified by:
MODEL1710260001.
To cite BioModels Database, please use:
Chelliah V et al. BioModels: ten-year
anniversary. Nucl. Acids Res. 2015, 43(Database
issue):D542-8.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
CC0
Public Domain Dedication for more information.
2020-03-20 | MODEL2001080001 | BioModels
Project description:APE1/Ref-1 protects cells from oxidative stress by acting as a central enzyme in base excision repair pathways of DNA lesions and through its independent activity as a redox transcriptional co-activator. To dissect between redox- and DNA-repair-mediated effects, here we performed transcription profiling of knock-in experiments using wild type and mutations C65S and 31-34A.
2011-10-01 | E-MEXP-2941 | biostudies-arrayexpress
Project description:Oxidative stress illustrates an imbalance between radical formation and removal. Frequent redox stress is critically involved in a variety of human pathologies including cancer, psoriasis, and chronic wounds. However, reactive species pursue a dual role being involved in signaling on the one hand and oxidative damage on the other. Using a HaCaT keratinocyte cell culture model, we here aimed at investigating the cellular and transcriptional response to periodic, low dose oxidative challenge over three months. Chronic redox stress was generated by frequent incubation with cold physical plasma treated cell culture medium. Using mRNA microarray technology, we found both acute ROS stress responses as well as numerous adaptions on the transcriptional level and over several weeks of redox challenge. This included an altered expression of 260 genes that function in inflammation and redox homeostasis, such as, signaling molecules, cytokines, and anti-oxidant enzymes. Apoptotic signaling was affected to a minor extend, especially in p53 down-stream targets. Strikingly, the anti-apoptotic heat shock protein HSP27 was strongly upregulated. These results suggest a variety of adaptive responses relating involved a number of cellular processes elicited by frequent redox stress over several months. They may help to better understand inflammatory responses in redox related diseases and possibly allow uncovering new biomarkers of ROS-stress. Microarrays were used to analyze and investigate the biological effects of repeated exposure of cold physical plasma on human HaCaT keratinocytes. Using an argon plasma jet kinpen, regulated transcripts were analyzed and further described in Schmidt et al. (submittes): âLong-term exposure to cold plasma-generated ROS âan in vitro model for redox-related diseases of the skinâ. HaCaT keratinocytes exposed to plasma treated medium - time course
2015-11-11 | E-GEOD-74876 | biostudies-arrayexpress
Project description:Breast cancer is a worlwide health problem. One of the factors involved in carcinogenesis is diet. Several studies indicate that resveratrol, a polyphenol present in diet, has several antitumor properties. The purpose of the study is gain an insight of resveratrol effect in cancer by determining the gene expression profile of breast cancer cell lines treated with the compound.
2011-08-01 | GSE25412 | GEO
Project description:Martinez-Guimera2017 - Generic negative feedback circuit (Model 4)
This model is described in the article:
'Molecular habituation' as a
potential mechanism of gradual homeostatic loss with age.
Martinez Guimera A, Welsh CM,
Proctor CJ, McArdle A, Shanley DP.
Mech. Ageing Dev. 2017 Nov; :
Abstract:
The ability of reactive oxygen species (ROS) to cause
molecular damage has meant that chronic oxidative stress has
been mostly studied from the point of view of being a source of
toxicity to the cell. However, the known duality of ROS
molecules as both damaging agents and cellular redox signals
implies another perspective in the study of sustained oxidative
stress. This is a perspective of studying oxidative stress as a
constitutive signal within the cell. In this work, we adopt a
theoretical perspective as an exploratory and explanatory
approach to examine how chronic oxidative stress can interfere
with signal processing by redox signalling pathways in the
cell. We report that constitutive signals can give rise to a
'molecular habituation' effect that can prime for a gradual
loss of biological function. This is because a constitutive
signal in the environment has the potential to reduce the
responsiveness of a signalling pathway through the prolonged
activation of negative regulators. Additionally, we demonstrate
how this phenomenon is likely to occur in different signalling
pathways exposed to persistent signals and furthermore at
different levels of biological organisation.
This model is hosted on
BioModels Database
and identified by:
MODEL1710260003.
To cite BioModels Database, please use:
Chelliah V et al. BioModels: ten-year
anniversary. Nucl. Acids Res. 2015, 43(Database
issue):D542-8.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
CC0
Public Domain Dedication for more information.
| MODEL1710260003 | BioModels